Abstract The PET imaging technique is one of a few available techniques that allow insight into the living brain, and PET using rat models has become an important tool in neuroscience. The Rat Conscious Animal PET scanner (RatCAP) is unique among small-animal PET scanners in that it eliminates the need for general anesthesia, and thus permits imaging of dynamic changes in brain activity while the animal experiences and acts on the environment. This is made possible by the scanner's miniature size which allows for direct attachment to the rat's head and significant freedom of movement. The overarching goal of this proposal is to explore the feasibility of using different PET radiotracers to assess acute changes in brain chemistry in the behaving rat. This is a critical step in bringing Brookhaven's mature RatCAP technology, developed over 8 years of Department of Energy support but no longer funded, into routine use in preclinical neuroscience. Specifically, we will experiment with three carbon-11 radiotracers: 11C-raclopride, an antagonist for dopamine D2 receptors (D2), 11C-(+)-PHNO, an agonist which binds specifically to the high affinity state of D2, and 11C-CNS-5161, an activity-dependent tracer which binds to NMDA receptors. Specific Aim 1 is to develop the 'bolus + infusion' radiotracer administration technique, which will maintain a steady-state condition of the tracer in the brain and detect perturbations from equilibrium. Specific Aim 2 is to test the radiotracers for their potential to reflect perturbations from equilibrium that are brought about by interventions with psychoactive drugs, including drugs of abuse. Specific Aim 3 is to use the 'bolus + infusion'technique to correlate changes in radiotracer equilibrium with changes in the behavior of rats that engage in sexual interactions. We hope that this proposal will result in the generation of first data that will mark the beginning of a new approach in the field of neuroscience. We envision that these data will allow for the formation of novel and specific hypotheses regarding the effects of natural and drug rewards on the brain that will then form the basis for long-term projects. 1